After balloon angioplasty, a metal tubular scaffold structure called a stent may be permanently implanted to physically hold open the repaired coronary artery. Unfortunately, up to 30% of such procedures result in narrowing or reclosure (restenosis) of the artery within six months to one year. One solution to the problem is to provide acute local, postoperative radiation treatment of the site using a catheter tipped with iridium-192 radioisotope. In this method, called intra-vascular brachytherapy, the iridium-192-tipped catheter is placed at the arterial site for thirty to forty minutes after stent deployment and then retracted. This type of acute high dose treatment using gamma radiation has been found to substantially reduce the rate of subsequent restenosis, as noted in Wiedermann, J. G. et al., "Intracoronary Irradiation Markedly Reduces Restenosis After Balloon Angioplasty in a Porcine Model," 23 J. Am. Coll. Cardiol., 1491-1498 (May 1994) and Teirstein, P. S. et al., "Catheter-Based Radiotherapy to Inhibit Restenosis After Coronary Stenting," 336 New England Journal of Medicine, 1697-1703 (Jun. 12, 1997).
This method of irradiating the patient suffers from the hazards associated with the required high radiation intensity. In addition to the surgeon, an oncologist and a radiation physicist are typically required for the procedure. A heavily shielded lead vault is needed to separate the patient from the operating room personnel, and the task of safely inserting the catheter containing the intense source, which is on the order of about 0.2 Curies, is particularly difficult. If irregularities occur in the procedure, the surgeon has relatively little time to respond, and therefore emergency procedures must be well-rehearsed. It is felt that this method, while possible in a research environment, may not be practical for normal usage.
An alternate method of addressing the restenosis problem is to use a permanently implanted radioactive stent, the method preferred by most physicians for its greater safety. Sources of radiation which are either pure beta particle or x-ray emitters are preferred because of the short range of the radiation, thus automatically protecting both the patient and the operating room personnel, particularly after the arterial insertion of the stent on the catheter.
As a result of studies in rabbits and swine, it is believed that a total dose of between 15 and 25 Grays is required to successfully inhibit restenosis in coronary arteries. Existing radioactive stent designs utilizing ion implantation of radioisotopes such as .sup.32 P, .sup.186 Re, .sup.90 Y or .sup.103 Pd require a highly specialized facility to perform the activations at considerable cost. U.S. Pat. Nos. 5,050,166 and 5,376,617 to Fischell et al. describe radioactive stents wherein radioactive material is either placed within the stent body or is electroplated onto the surface. Other methods involving cyclotron irradiation or coatings with radioactive liquids have contamination and safety problems respectively. Handling radioactive materials in these methods is difficult, expensive, and risky.
To avoid such difficult procedures, it is possible to ion-implant or coat a stent with a stable isotope, such as .sup.31 P, .sup.185 Re, .sup.89 Y, or .sup.102 Pd, which can be activated by neutron bombardment in order to generate a radioisotope, such as .sup.32 P, .sup.186 Re, .sup.90 Y, or .sup.103 Pd, respectively. In this manner, the stent would be fabricated in the absence of any radioactive species and then activated prior to implantation into the patient. The material used for the body of the stent to be activated must be carefully selected not to include elements that are easily activated by neutron bombardment to produce isotopes that give off undesirable radiation. For example, stainless steel, an otherwise ideal material, cannot be used in the above method because the neutron bombardment will activate the stent body to produce long-lived, high-energy gamma ray-emitting isotopes such as .sup.51 Cr and .sup.59 Fe, which are unacceptable in a permanently implanted stent.
Even small impurities in otherwise acceptable metals may give rise to harmful radiation. For example, Laird ("Inhibition of Neointinol Proliferation with Low-Dose Irradiation from a .beta.-Particle-Emitting Stent", Laird J. R. et al., Circulation, 93, No. 3, February 1996) ion-implanted a titanium stent with stable .sup.31 P and generated the radioisotope .sup.32 P by inserting the ion-implanted stent in a nuclear reactor. This technique produced only a very small amount of .sup.32 P, and the trace impurities in the titanium body produced high energy gamma rays which were comparable in strength to the desired .sup.32 P radiation. This technique suffered from the fact that .sup.31 P has a very small neutron activation cross-section (0.18 barns), and thereby requires a long activation time. Even though titanium itself does not activate with thermal neutrons to form long-lived radioisotopes, titanium does activate with fast neutrons to .sup.46 Ti, having a long half-life of 83 days, and the high cross-section impurities in the titanium body produced too much harmful contaminating gamma radiation. These experiments on titanium stents suggest that ion implantation of stable isotopes into stainless steel stents would present even greater obstacles.